The broad long term goal of this project is to empower women to protect themselves from HSV and HIV infection through the development of an HSV microbicide based on sustained release drug delivery. Each day 15,000 people are infected with HIV- a growing majority of them women. Fifty million Americans are infected with genital herpes, and the disease is common in areas of the world of high HIV prevalence. Because genital herpes dramatically increases the transmissibility of HIV programs, the development of an effective method to reduce the spread of HSV is of high programmatic relevance to the NIH as well as other world health organizations. We have developed a platform technology for the sustained release of a broad range of drugs by implantation which maintains antiviral levels for long periods. This technology lead to the ganciclovir intraocular implant: the Vitrasert(R), approved for the treatment of AIDS related CMV retinitis. We propose to utilize this platform to develop sustained release vaginal ring formulations for acyclovir. We have formulated prototype rings that release acyclovir in a linear fashion over 30 days. In this Phase 1 project we propose to formulate and test sustained release acyclovir implants in vitro and then test their safety and efficacy in an established animal model. PUBLIC HEALTH RELEVANCE: Infection with genital herpes dramatically increases the risk of the spread of HIV. The broad long term goal of this project is to protect women currently uninfected by genital herpes from infection by developing an effective intravaginal ring microbicide based on the sustained release drug delivery of acyclovir. We will formulate prototype intravaginal devices for use in animals, confirm the safety and delivery of acyclovir over prolonged periods, and test the hypothesis that topical acyclovir can prevent infection in an animal model. The successful incorporation of acyclovir into a ring based microbicide could have a dramatic impact on the evolution of the AIDS pandemic.